Defining the mechanistic contributions to meal induced drug plasma level variability may offer both formulation and drug design solutions toward reducing fed-versus fasted-state absorption variability and maximizing oral bioavailability. The long-range goal of our research is to determine the mechanisms by which the co-administration of meals with orally administered, weakly basic drugs alters their absorption and oral bioavailability from administration under fasted-state conditions. The immediate goal of these studies is to determine the mechanisms by which meal intake decreases the oral bioavailability of the protease inhibitor, indinavir (Drixivan), and increases that of ritonavir (Norvir) as compared to fasted-state administration.